Significance of CD 105 expression for tumour angiogenesis and prognosis in endometrial carcinomas.
ABSTRACT Angiogenesis is a key process in tumour growth and metastasis, and Factor-VIII microvascular density has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to activated endothelial cells in tissues participating in angiogenesis, and we therefore wanted to compare the prognostic significance of CD105/endoglin to that of Factor-VIII. In a population-based endometrial carcinoma study with long (median 11.5 years) and complete patient follow-up, mean intratumour microvascular density (MVD) assessed using CD105/endoglin was investigated and compared with previous data for MVD assessed using Factor-VIII. MVD by CD105/endoglin was significantly correlated with MVD by Factor-VIII (p=0.001). However, tumours within the two groups defined by the upper and lower quartiles for CD105/endoglin-MVD were both significantly more often metastatic (FIGO-stage III/IV; p=0.03), with high tumour cell proliferation by Ki67 (p=0.007) and with reduced survival (p=0.036) as compared with the intermediate groups. In Cox regression analysis, CD105/endoglin-MVD showed independent prognostic influence when analysed together with patient age, FIGO stage, histologic subtype, histologic grade and Factor-VIII-MVD, while the latter lost its prognostic impact when CD105/endoglin was included. In the subgroup with high MVD, there was a tendency towards improved response to radiation therapy. In conclusion, CD105/endoglin-MVD is significantly associated with FIGO stage, tumour proliferation and prognosis in endometrial carcinoma, indicating that this is a better angiogenic marker in these tumours.
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ABSTRACT: Bladder cancer (BC) is a serious medical problem. The high rate of recurrence and progression demands the development of new methods, such as genetic markers, which allow diagnosis and patient follow-up. The aim of this study was to compare expression of HIF-1, GLUT1, endoglin, and BRIC5 in patients without and those with BC. The second group was divided into sub-groups: those without a history of PDD (photodynamic diagnosis) in the diagnostic process and those after PDD. Patients with BC were diagnosed using the PDD method using hexaminolevulinate (Hexvix(®)). The expressions of HIF-1, GLUT1, endoglin, and BRIC5 genes were established in urine specimens by real-time quantitative polymerase chain reaction (PCR). The expressions of all tested genes were higher in the group of patients with BC than in the group without BC. In the group after PDD, a statistically significant overexpression of HIF-1 was observed. In this group, changes were not observed in cases of the other three tested genes. The differences between the group with PDD and the group without it can be connected with the direct influence of PDD on malignant tissue, which can cause overexpression of HIF-1 only. This is, however, only a hypothesis and needs further study.Central European journal of urology. 01/2012; 65(3):146-50.
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ABSTRACT: Preoperative evaluation of the risk for metastases in endometrial carcinoma is challenging. The growth of new vessels, angiogenesis, is important for tumor growth and purported to be involved in the metastatic process. The aim of this study was to evaluate the significance of preoperative serum levels and immunohistochemical expression of angiogenic markers in predicting a metastasized disease. Preoperative sera from 98 consecutive women presenting with endometrial carcinoma were collected. Serum concentrations of VEGF, sFLT1, and CD105 were assessed by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to assess the expression of CD105, VEGF, FLT1, and KDR. The results were correlated to the presence of metastases, presence of deep (≥50 %) myometrial invasion, and the histological grade of the tumor. Tumors with other than endometrioid histology were excluded. Of the 80 evaluable patients, 11 had a metastasized disease. The serum concentration of VEGF was higher in the group with metastases than in the group without metastases (median [range], 743 pg/mL [546-1,183 pg/mL] vs. 383 pg/mL [31-1,524 pg/mL], p < 0.001, respectively). In the multivariable analysis, the concentration of VEGF was the sole independent, albeit weak predictive factor for the presence of metastases (odds ratio, 1.004, 95 % confidence interval, 1.002-1.007; p = 0.001). The immunohistochemical expression of the markers was not associated with any of the clinicopathological features of the tumors. The results of the present study suggest that preoperative serum VEGF concentration correlates with the presence of metastases in endometrioid endometrial carcinoma.Tumor Biology 01/2014; · 2.52 Impact Factor
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ABSTRACT: This article reviews the main prognostic and predictive biomarkers of endometrial (EC) and ovarian carcinoma (OC). In EC, prognosis still relies on conventional pathological features such as histological type and grade, as well as myometrial or lymphovascular space invasion. Estrogen receptor, p53, Ki-67, and ploidy analysis are the most promising biomarkers among a long list of molecules that have been proposed. Also, a number of putative predictive biomarkers have been proposed in molecular targeted therapy. In OC, prognosis is predominantly dependent on disease stage at diagnosis and the extent of residual disease at primary operation. Diagnostic markers which aid in establishing histological type in OC are available. However, not a single universally accepted predictive or prognostic marker exists to date. Targeted therapy has been growingly focused at in recent years, in view of the frequent development of chemoresistance at recurrent disease. The present review emphasizes the crucial role of correct pathological classification and stringent selection criteria of the material studied as basis for any evaluation of biological markers. It further emphasizes the promise of targeted therapy in EC and OC, while simultaneously highlighting the difficulties remaining before this can become standard of care.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 02/2014; · 2.68 Impact Factor